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Am J Respir Cell Mol Biol. 2019 Feb;60(2):158-166. doi: 10.1165/rcmb.2018-0021OC.

The Effects of IFN-λ on Epithelial Barrier Function Contribute to Klebsiella pneumoniae ST258 Pneumonia.

Author information

1
Department of Pediatrics, Columbia University College of Physicians and Surgeons, New York, New York.

Abstract

IFN-λ and IL-22, cytokines that share the coreceptor IL-10RB, are both induced over the course of Klebsiella pneumoniae ST258 (KP35) pneumonia. IL-22 is known to protect mucosal barriers, whereas the effects of IFN-λ on the mucosa are not established. We postulated that IFN-λ plays a role in regulating the airway epithelial barrier to facilitate cellular trafficking to the site of infection. In response to IFN-λ, the transmigration of neutrophils across a polarized monolayer of airway epithelial cells was increased, consistent with diminished epithelial integrity. KP35 infection increased epithelial permeability, and pretreatment with IFN-λ amplified this effect and facilitated bacterial transmigration. These effects of IFN-λ were confirmed in vivo, in that mice lacking the receptor for IFN-λ (Ifnlr1-/-) were protected from bacteremia in a murine model of KP35 pneumonia. Conversely, the integrity of the epithelial barrier was protected by IL-22, with subsequent impairment of neutrophil and bacterial transmigration in vitro. Maximal expression of IL-22 in vivo was observed later in the course of infection than IFN-λ production, with high levels of IL-22 produced by recruited immune cells at 48 hours, consistent with a role in epithelial barrier recovery. The divergent and opposing expression of these two related cytokines suggests a regulated interaction in the host response to KP35 infection. A major physiological effect of IFN-λ signaling is a decrease in epithelial barrier integrity, which facilitates immune cell recruitment but also enables K. pneumoniae invasion.

KEYWORDS:

; IFN-λ; IL-22; airway epithelial barrier; bacterial pneumonia

PMID:
30183325
PMCID:
PMC6376406
[Available on 2020-02-01]
DOI:
10.1165/rcmb.2018-0021OC

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